The undesirable biological effects of phthalate esters (the most ubiquitous of all environmental pollutants), which include acute testicular atrophy resulting in male sterility, hepatocarcinogenesis in rats and mice, and proliferation of peroxisomes, are mediated through their metabolites. We have identified some 27 metabolites of the most widespread phthalate, di(2-ethylhexy)phthalate (DEHP), have postulated a metabolic pathway for their formation, have confirmed and detailed the first two steps in the pathway, and have formed an hypothesis as to the part of the pathway responsible for the dramatic differences in metabolic profiles in different species. As the biological activities of the different metabolites are elucidated, it becomes clear that species differences in metabolism can potentially result in resistance of non-rodent species to the undesirable biological effects. This makes extrapolation of toxicity tests from rodents to man highly unreliable, even though we have also provided evidence for general internalized exposure of humans to phthalate esters.